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Therapeutic antibodies: successes, limitations and hopes for the future.

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TLDR
An overview of the current state of the art of monoclonal antibodies is given and the most promising avenues that are being followed to create the next generation of antibody‐based therapeutic agents are described.
Abstract
With more than 20 molecules in clinical use, monoclonal antibodies have finally come of age as therapeutics, generating a market value of $11 billion in 2004, expected to reach $26 billion by 2010. While delivering interesting results in the treatment of several major diseases including autoimmune, cardiovascular and infectious diseases, cancer and inflammation, clinical trials and research are generating a wealth of useful information, for instance about associations of clinical responses with Fc receptor polymorphisms and the infiltration and recruitment of effector cells into targeted tissues. Some functional limitations of therapeutic antibodies have come to light such as inadequate pharmacokinetics and tissue accessibility as well as impaired interactions with the immune system, and these deficiencies point to areas where additional research is needed. This review aims at giving an overview of the current state of the art and describes the most promising avenues that are being followed to create the next generation of antibody-based therapeutic agents. This article is part of a themed section on Vector Design and Drug Delivery. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009

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References
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Journal ArticleDOI

Continuous cultures of fused cells secreting antibody of predefined specificity

TL;DR: The derivation of a number of tissue culture cell lines which secrete anti-sheep red blood cell (SRBC) antibodies is described here, made by fusion of a mouse myeloma and mouse spleen cells from an immunised donor.
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Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface

TL;DR: Foreign DNA fragments can be inserted into filamentous phage gene III to create a fusion protein with the foreign sequence in the middle that is incorporated into the virion, which retains infectivity and displays the foreign amino acids in immunologically accessible form.
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Phage antibodies: filamentous phage displaying antibody variable domains

TL;DR: It is shown that complete antibody V domains can be displayed on the surface of fd bacteriophage, that the phage bind specifically to antigen and that rare phage can be isolated after affinity chromatography.
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Naturally occurring antibodies devoid of light chains

TL;DR: The presence of considerable amounts of IgG-like material of Mr 100K in the serum of the camel, which is composed of heavy-chain dimers and devoid of light chains, but nevertheless have an extensive antigen-binding repertoire, opens new perspectives in the engineering of antibodies.
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Replacing the complementarity-determining regions in a human antibody with those from a mouse

TL;DR: This work substituted the CDRs from the heavy-chain variable region of mouse antibody B1–8, which binds the hapten NP-cap, for the corresponding CDRs of a human myeloma protein, to determine whether the antigen-binding site could be transplanted from one framework to another by grafting theCDRs.
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